The present invention relates to a process for preparing hydrochloride of 3-acetoxy-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-b enzothiazepin-4(5H)-one which is useful as a medicinal compound.
Hydrochloride of 3-acetoxy-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-b enzothiazepin-4(5H)-one (hereinafter referred to as desired compound), particularly, d-cis form thereof is a medicinal compound useful as a coronary vasodilator and an anti-hypertensive agent. Hitherto, there have been known some processes for preparing the desired compound. Examples of these processes are, for instance, (1) a process wherein 3-hydroxy-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-b enzothiazepin-4(5H)-one (hereinafter referred to as 3-hydroxy compound) is reacted with an acetylating agent such as acetic anhydride with heating to give 3-acetoxy-2,3-dihydro-5-[2-(dimethylamino)ethyl]-2-(p-methoxyphenyl)-1,5-b enzothiazepin-4(5H)-one (hereinafter referred to 3-acetoxy compound) according to a conventional method and then the resulting 3-acetoxy compound is treated with ethanolic hydrogen chloride (or methanolic hydrogen chloride) (see Japanese Examined Patent Publication No. 813/1972 and No. 18038/1978), (2) a process wherein the 3-hydroxy compound is reacted with acetic anhydride in the presence of hydrochloric acid in one step (see Japanese Unexamined Patent Publication No. 132876/1987) and the like.
However, in the process (1), two steps, namely, a step for the acetylation and a step for the formation of hydrochloride, are required to be carried out separately, although the acetylation can be suitably carried out in the absence of water. On the other hand, in the process (2), hydrochloric acid must be at first added with cooling and then the acetylation is carried out with heating, since heat is generated on the addition of hydrochloric acid (aqueous solution of hydrogen chloride) used as a supplier of hydrogen chloride. The operations in the method (2) are, therefore, complicated. Further, it is always required in the method (2) to use a large exess of acetic anhydride for removing water existing in the reaction system, which is introduced on the addition of hydrochloric acid, since the acetylation cannot be completed in the presence of water.
An object of the invention is to provide a process for simply preparing the desired compound from the 3-hydroxy compound in one step without cooling the reaction system or using a large excess of an acetylating agent.
This and the other objects of the present invention will become apparent from the description hereinafter.